Lab Notes: What Were We Talking About?

A brain protein apparently mediating age-related memory loss (distinct from neurodegenerative disease) holds promise for keeping "senior moments" at bay. Also this week: new tricks from an old drug.

Memory Loss Linked to ... Uh ...

A single protein in one region of the brain may be responsible for age-related memory loss, according to researchers led by Nobel laureate Eric Kandel, MD, of Columbia University Medical Center in New York City. A series of experiments in mice suggests that levels of RbAp48 in the dentate gyrus of the hippocampus fall with age, leading to memory impairment.

The dentate gyrus has been implicated in age-related memory impairment. In a human genetic study, Kandel and colleagues found 17 genes the transcription of which varied with age, chief among them the gene for RbAp48, which plays multiple roles in histone acetylation and transcription regulation.

In subsequent lab experiments, young mice with the protein turned off had memory impairment similar to that seen in aged animals, but when the protein was turned on again, their memories returned to normal. Even better, replacing the protein in aged mice restored their ability to remember, the investigators reported in Science Translational Medicine.

One implication of the finding is that age-related memory loss is a syndrome in its own right, separate from dementias such as Alzheimer's, disease Kandel said in a statement. Another is that such memory loss can potentially be the subject of therapy with compounds that stimulate RbAp48 or one of the pathways it's involved in, he said.

-- Michael Smith

An Old Drug With New Immune Tricks

A cancer drug originally developed in the 1960s has immunosuppressant potential for transplant patients and those with autoimmune diseases, according to researchers from Lund University in Sweden.

Zebularine is a DNA demethylating agent that can induce the expression of two specific immunosuppressive enzymes, indolamine-2,3-deoxygenase-1 and kynureninase. To see if this action could be exploited therapeutically, Leif G. Salford, MD, PhD, and colleagues induced diabetes in a group of rats through injections of streptozotocin, and then grafted islets of Langerhans into the subcapsular space of the kidney. Half of the animals were then treated with zebularine for 14 days and the other received no treatment.

The rats given zebularine remained normoglycemic for a mean of 67 days compared with only 2 weeks among controls. In addition, half of the treated rats still had normal glucose levels after 3 months but subsequently developed hyperglycemia after nephrectomy, suggesting recovery of pancreatic function.

This long-lasting immune suppression was limited to the target cells and therefore might avoid activating the immune system at large, which leaves patients at risk of infections and cancer, the researchers explained in PLOS One.

-- Nancy Walsh

A Shot Against Noise-Related Hearing Loss?

Loud noise activates certain cells in the inner ear that detach and damage the endothelial fluid barrier in blood vessels, but boosting levels of the protein they modulate reduces the hearing loss it causes, researchers found in an animal study.

Mice exposed to 120 db -- the level of a loud rock concert or jet engine -- for several hours 2 days in a row showed changes in a type of macrophage that modulates proteins in the inner ear to maintain hearing. The cells physically detached from capillary walls, resulting in proteins leaking out of the damaged vascular barrier.

But an injection of the signaling molecule of those cells restored barrier integrity and hearing lost from the noise damage, Xiaorui Shi, MD, PhD, of the Oregon Health and Science University in Portland, and colleagues reported in the FASEB Journal.

"It's easy to say that we should avoid loud noises but, in reality, this is not always possible," Gerald Weissmann, MD, editor-in-chief of the journal, commented in a statement. "Front-line soldiers or first responders do not have time to worry about the long-term effects of loud noise when they are giving their all. If, however, a drug could be developed to minimize the negative effects of loud noises, it would benefit one and all."

-- Crystal Phend

Collagen for an Ailing Heart

Researchers have developed a collagen patch that can help repair the protective outer layer of the heart, according to Vahid Serpooshan, PhD, of Stanford University School of Medicine, and colleagues.

The patch, which is made of structurally-modified collagen, can be grafted onto heart tissue and rather than replacing dead muscle cells, replaces the epicardium to protect and support the myocardium.

Mouse studies have shown that damaged hearts grafted with the collagen patch had speedier generation of new cells and blood vessels in the affected area, they wrote online in the journal Biomaterials.

Mice in the study were given a surgically-induced heart attack. Those getting the patch had significant improvement in overall cardiac function and in echocardiograms 2 weeks later, and new cells proliferated around the patch and surrounding damaged heart tissues. Damaged hearts treated with the patch also had greater development of new blood vessels.

The patch is made of a cell-free collagen, which means a recipient does not require immunosuppression, and the collagen is later absorbed into the organ, the researchers pointed out.

They also noted that the patch might be used to deliver medications or stem cells to a patient.

-- Cole Petrochko

Gut's Sugar Sensors Impaired in Diabetes

"Sweet taste" receptors in the gut may be impaired in patients with type 2 diabetes, potentially leading to an increased risk of hyperglycemia after a meal, researchers found.

In a small study, expression in the gut of the sweet taste receptor T1R2 fell off 30 minutes after a glucose infusion in healthy patients, but rose in patients with type 2 diabetes, Richard Young, PhD, of the University of Adelaide, and colleagues reported online in Diabetes.

That could indicate a faulty "braking" system for glucose absorption in patients with type 2 diabetes, potentially exacerbating postprandial hyperglycemia.

"This shows that diabetes is not just a disorder of the pancreas and of insulin," Young said in a statement. "The gut plays a bigger role than researchers have previously considered."

For their study, the researchers took endoscopic biopsies of the duodenum in 14 healthy patients and 13 type 2 diabetes patients at baseline and then 30 minutes after a glucose infusion.

They found that expression of T1R2 in the gut fell off a half hour after the infusion in healthy patients, but rose in those with type 2 diabetes -- leading to greater glucose absorption in these patients, they reported.

"By gaining a better understanding of how these mechanisms in the gut work, we hope that eventually this will assist to better manage or treat diabetes in the future," Young said.

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